Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci within 1.12 Mb and 1.25 Mb Intervals on Chromosome 3

Substitution mapping was used to refine the localization of blood pressure (BP) quantitative trait loci (QTLs) within the congenic region of S.R-Edn3 rats located at the q-terminus of rat chromosome 3 (RNO3). An F2(SxS.R-Edn3) population (n=173) was screened to identify rats having crossovers within the congenic region of RNO3 and six congenic substrains were developed that carry shorter segments of R-rat derived RNO3. Five of the six congenic substrains had significantly lower BP compared to the parental S rat. The lack of BP lowering effect demonstrated by the S.R(ET3x5) substrain and the BP lowering effect retained by S.R(ET3x2) substrain, together define the RNO3 BP QTL-containing region as approximately 4.64 Mb. Two non-overlapping substrains, S.R(ET3x1) and S.R(ET3x6), had significantly lower BP compared to the S strain, indicating the presence of two distinct BP QTLs in the RNO3 q-terminus. The RNO3 q-terminus was fine-mapped with newly developed polymorphic markers to characterize the extent of the congenic regions. The two RNO3 BP QTL regions were thus defined as within intervals of 0.05-1.12 Mb and 0.72-1.25 Mb, respectively. Also important was our difficulty in fine-mapping and marker placement in this portion of the rat genome (and thus candidate gene identification) using the available genomic data, including the rat genome sequence.

Key Words: Dahl salt-resistant rat, Dahl salt-sensitive rat, genetic hypertension, inbred rat strains, salt-sensitivity

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